The Epstein-Barr virus (EBV) is considered a possible major factor in the etiology of some human cancers. The bulk of the early evidence for these associations came from immunological studies utilizing cells expressing a variety of EBV-associated antigens. These studies have also been important for identifying antibodies to certain antigens that appear to be of potential diagnostic and prognostic importance in these diseases and those antigens responsible for inducing immunity to the virus and virus-infected or transformed cell. There has been little progress in the purification and characterization of these antigens. This laboratory has been concentrating on the purification of the EBV-induced membrane antigen (MA) complex primarily because of its importance in immunity. The current studies are directed at (1) the further purification and biochemical characterization of the major MA glycoproteins. This will include the characterization of the carbohydrate moieties of the different glycoproteins as well as analysis of the protein components; (2) the production of both mouse and human monoclonal antibodies to these glycoproteins which will be important for the purification and biological characterization of such glycorproteins and for looking for strain differences; (3) analysis of sera from patients with different EBV-associated diseases for antibodies to different EBV-MA antigenic determinants to determine if any of these show a disease association and to attempt to further identify those determinants involved in neutralization and antibody-dependent cellular cytotoxicity (ADCC); and (4) to assess the value of purified MA components as subviral vaccines against EBV infections. Such studies should lead to a better understanding of the nature of those antigens involved in the induction of the various arms of immunity against EBV-induced disease manifestations.